NovaScreen Biosciences Corp. has successfully completed a Phase I SBIR project (#1 R43 AA014542-01, entitled "Novel Molecules to Treat Alcoholism") and is submitting this Phase II SBIR application in response to RFA-AA-04-002, "Medications Development to Treat Alcoholism." The specific objective of this Phase II application is to discover and to advance at least one novel, optimized, new chemical entity (NCE) up to the stage of preclinical development. That NCE will be designed to be concurrently active at multiple (two) molecular targets, each a validated drug target for treating alcoholism. Compounds active at multiple targets may have greater therapeutic efficacy than agents acting at single targets, and display fewer side effect liabilities than cocktails of two or more different drugs each active at single targets. Our Phase I SBIR research has produced a promising lead compound and an array of structure-activity relationship (SAR/QSAR) models of small molecules that concurrently modulate the serotonin 5HT3 receptor and the mu-opioid receptor. Additionally, we also produced SAR/QSAR models for compounds that display dual activity at 5HT3 and at other opioid receptor subtypes (i.e., 5HT3-delta opioid and 5HT3-kappa opioid). Our emphasis in this Phase II builds on Phase I results and employs these SAR/QSAR models to continue optimization and development of the identified lead compound to produce a new generation of therapeutic candidates for the treatment of alcohol dependency. [unreadable] [unreadable]